The combined international efforts of two major genomics collaboratives — both led by UCSF faculty — have discovered ten times more genes that contribute to obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD), including Tourette disorder (also known as Tourette syndrome), than previously known. This work, published Sept. 1, 2026, in the journal Nature Neuroscience, provides critical insight into the molecular origins of both syndromes, hurdling a major roadblock in the path to developing novel, more effective treatments.
Researchers from across the United States participating in a study of OCD genomics, supported by the Foundation for OCD Research (FFOR), collaborated with colleagues in Europe, Canada, and South Korea in the NIH-supported Tourette International Genetics Study Consortium (TICGen) to identify 36 “large-effect” genes underlying both disorders. These genes provide critical starting points for understanding pathobiology and ultimately developing targeted therapies. Prior efforts over the past decade had found only four large-effect genes across both OCD and CTD.
These findings vastly expand our understanding of contributing genetic factors to two potentially disabling conditions which frequently occur together and affect millions of individuals worldwide. While there have been significant advances over the past decade in understanding brain circuits involved in both conditions, their molecular roots have remained a near total mystery. The expanded molecular map created by this work lays the groundwork for targeted medications that could complement ongoing advances in neuro-sensing and neuromodulation techniques, offering a multi-targeted approach to treating OCD and tic disorders.
“Going from four high-confidence genes to more than 30 completely changes the game in terms of our ability to take the next steps in finding what is causing these disorders at a molecular level,” said Belinda Wang, MD, PhD, an assistant adjunct professor in the UCSF Department of Psychiatry Behavioral Sciences and first author on the paper. “It was surprising to discover that several of the mutated genes encode extracellular matrix proteins —the structural scaffolding surrounding cells that helps shape brain wiring and neuroplasticity. We are already moving forward with collaborators at UCSF studying the proteins these genes make to understand why and how disruptions may lead to OCD and/or CTD.”
New findings build on years of previous work
The report represents the culmination of nearly two decades of research aimed at uncovering the genetic causes of Tourette and OCD. Both the TICGen and FFOR genomics initiatives were co-founded by Matthew W. State, MD, PhD, the Oberndorf Family Distinguished Professor and chair of the UCSF Department of Psychiatry and Behavioral Sciences. Associate Adjunct Professor Jeremy Willsey, PhD, co-led both initiatives, and UCSF Associate Professor Moses Lee, MD, PhD, co-led the FFOR effort.
Prior genomic analyses by State and Willsey, as part of the TICGen consortium, identified the first two CTD “high-confidence” large-effect genes in 2017. The inclusion of OCD and the dramatic increase in the number of genes discovered in the current study were the result of bringing TICGen together with FFOR’s broad effort to advance research in OCD, led by Stanford University's Robert C. Malenka, MD, PhD. “This work is a powerful proof of concept that combining genetically related cohorts dramatically expands risk gene discovery, opening up new opportunities to uncover the biology driving these conditions,” said Wang.
“Identifying these risk genes provides the essential entry point we’ve been waiting for,” said Willsey, who is also the director of translational data science at Calico Life Sciences. “Now that we have these molecular targets in hand, we can leverage advanced informatics, large-scale datasets, and hypothesis-driven experiments to map how their disruption impacts brain development and function—and ultimately, accelerate the path toward actionable therapies.”
“It has taken the extraordinary commitment on the part of patients and their families, a lot of hard work across labs, and a long time to get to here,” noted State, “but it is truly an inflection point and the road ahead is extremely exciting. The pace at which the understanding of genetics can now be translated into the development of new treatment targets is remarkable and OCD and CTD are now primed for making this leap.”
Additional contributors to the work at UCSF include Matt Tran, PhD; Sheng Wang, PhD; Linda Chow, PhD; George Wang; Nawei Sun, PhD; Jeanselle Dea; Starlette Khim; Allison Libby, PsyD; Tenzin Norbu; and Nevan Krogan, PhD.
